System for forming and modifying lenses and lenses formed thereby

ABSTRACT

A lens for placement in a human eye, such as intraocular lens, has at least some of its optical properties formed with a laser. The laser forms modified loci in the lens when the modified loci have a different refractive index than the refractive index of the material before modification. Different patterns of modified loci can provide selected dioptic power, toric adjustment, and/or aspheric adjustment provided. Preferably both the anterior and posterior surfaces of the lens are planar for ease of placement in the human eye.

CROSS-REFERENCE

This application is a division of co-pending U.S. patent applicationSer. No. 13/030,958 filed on Feb. 18, 2011, which in turn is a divisionof U.S. patent application Ser. No. 12/717,886 filed on Mar. 4, 2010(now U.S. Pat. No. 8,292,952), which claims the benefit of provisionalapplication Ser. Nos. 61/209,362 filed Mar. 4, 2009; 61/209,363 filedMar. 4, 2009; 61/181,420 filed May 27, 2009; 61/181,519 filed May 27,2009; and 61/181,525 filed May 27, 2009. These provisional applicationsare incorporated herein by this reference. To the extent the followingdescription is inconsistent with the disclosures of the provisionalapplications, the following description controls.

BACKGROUND

Lenses are implanted in eyes to improve vision. In general there are twotypes of intraocular lenses. One type replaces the eye's natural lens,usually to replace a cataractous lens. The other type is used tosupplement an existing lens and functions as a permanent correctivelens. Replacement type of lenses are implanted in the posterior chamber.A supplemental type of lens, referred to as a phakic IOL (intraocularlens), is implanted in the anterior or posterior chamber to correctrefractive errors of the eye.

There are two common techniques used for forming intraocular lenses. Onetechnique is molding, where an optical polymeric material is formed intoa desired shape having a predetermined dioptic power. These lenses areavailable in standard diopter powers, typically differing in about 0.5diopter power. A problem with the molding technique is it is a veryexpensive way to make a customized lens, and thus for most patients,only an approximate approach to clear vision is obtained. For somepatients the diopter power can be wrong by 0.25 or more. Moreover, suchlenses generally are not as effective for patients who have anabnormally shaped cornea, including some that have undergone a corneaprocedure, such as LASIK surgery.

The other technique used is lathing and milling, where a disc shapedlens blank is ground to a desired shape. Due to the properties of thematerials used for intraocular lenses, it is preferable to machinelenses at a reduced temperature such as −10° F. A problem with lathingand milling is that the optical properties of a lens at −10° F. may bedifferent than the optical properties of the lens at body temperature,and thus such a lens only approximates optimal vision. In addition, asthe lens warms it absorbs moisture and dimensions of the lens maychange, thus altering the diopter power of the lens.

For some patients, it is desirable that the lenses be aspheric tocorrect corneal spherical aberrations or toric to correct or mitigatecorneal astigmatism over a range of diopters. Commercially availableIOLs generally cannot uniformly correct these optical defects because itwould be necessary to inventory hundreds, if not thousands, of differenttypes of lenses, all varying in dioptic power, and aspheric and toricfeatures.

Another problem associated with conventional manufacturing techniques isthat the lens often cannot accommodate the needs of patients that haveundergone a LASIK (laser assisted in situ keratomileusis) surgery. LASIKsurgery can correct for myopia, hyperopia, and/or astigmatism. However,alterations in the cornea created in the LASIK procedure make it verydifficult to find an IOL with the appropriate adjustment forasphericity. A conventional IOL is generally not satisfactory forpatients that have undergone a LASIK procedure or with an abnormalcornea, because of the challenge in inventorying IOLs suitable for sucha patient.

A technique for modifying the refractive index of an optical polymericmaterial such as in an IOL is discussed in Knox et al., U.S. PublicationNo. 2008/0001320. This technique uses a laser for changing therefractive index of small areas of an optical material, resulting inchanges in refractive index of up to about 0.06, which is an inadequatechange in diopter power for most applications.

Accordingly, there is a need for a system for forming intraocular lensesthat overcomes the disadvantages of prior art manufacturing techniques,and also allows for customization of lenses to provide multiplecorrective features to approach optimum vision, including for patientsthat have had a LASIK procedure.

SUMMARY

The present invention provides a system that meets this need, and alsoprovides lenses formed and modified by this system. A lens formed bythis system has unique properties. The lenses typically are IOLs, butthe invention has other applications, as discussed below. A lensaccording to this invention comprises a body formed of an opticalmaterial having a refractive index. The body has opposed interior andposterior surfaces, and an optical axis. The body contains modifiedloci. The modified loci have been formed by a laser beam and have adifferent refractive index than the material before modification. Thelens has many unique features, and can be characterized by having atleast one of the following features, all of the following features, orany combination of the following features:

-   -   (i) sufficient modified loci in the body so that the refractive        index of the body has been modified sufficiently to change the        diopter power of the body by at least plus or minus 0.5 (i.e., a        positive diopter power change of at least 0.5 or a negative        diopter power change of −0.5 or more such as −10;    -   (ii) at least some of the modified loci have an optical path        length of from 0.1 to about 1 wave greater than the optical path        length of a non-modified locus, wherein the wavelength is with        respect to light of wavelength of 555 nm;    -   (iii) at least some of the modified loci are in a substantially        circular pattern around the optical axis;

(iv) sufficient modified loci that at least 90% of light projected ontothe anterior surface in a direction generally parallel to the opticalaxis passes through at least one modified locus;

-   -   (v) at least some of the modified loci are right cylindrical in        shape with an axis substantially parallel to the optical axis        and a height of at least 5 μm;    -   (vi) both the posterior and anterior surfaces are substantially        planar; and    -   (viii) each modified locus has a depth of from 5 to 50 μm.

Typically there are at least 1,000,000 or more modified loci located ina first layer of the body, the first layer being substantially parallelto the anterior surface, where the layer is about 50 μm thick. Acircular pattern, referred to as an annular ring pattern, of modifiedloci can be used.

When the modified loci are used to obtain a desired optical effect, andmore conventional constructions are not used, then preferably there aresufficient loci that at least 99% of the light projected onto theanterior surface of the body in a direction generally parallel to theoptical axis passes through at least one modified loci. Thussubstantially all optical effects provided by a lens can be provided bythe modified loci.

The lens can provide a dioptic power adjustment, and can also be usedfor providing toric adjustment and/or aspheric adjustment.

An advantage of the present invention is the body of the lens can bemade very thin, in the order from about 50 to about 400 μm maximumthickness, which allows for easy insertion into the posterior chamber ofan eye in the case of an intraocular lens. This also allows a physicianto make a smaller incision in the eye than is possible with installingconventional intraocular lenses. Preferably the maximum thickness of thebody is about 250 μm.

An advantage of the version of the invention where both the anterior andposterior surfaces are substantially planar is there are no features onthe body that can interfere with placement of an IOL in the posteriorchamber of the eye.

Typically the modified loci have a depth of from about 5 to about 50 μm.Each modified loci can have from 1 to 10 sites, each site typicallybeing formed by a sequence of about 100 infrared laser pulses in asingle burst focused on a single spot, i.e., site. At least some of themodified loci can be contiguous to each other.

There can be multiple layers of modified loci, where each layer can havea thickness of about 50 μm. Typically the layers are spaced apart fromeach other by about 5 μm.

In the multiple layer version of a lens, at least some of the modifiedloci in the first layer can have an optical path length of at least 0.1wavelength greater than the optical path length of a non-modified locus,where the wavelength with respect to the light of a first wavelength.The second layer can have modified loci having an optical path length ofat least 0.1 wavelength greater than the optical path length ofnon-modified locus, with respect to the light of a second wavelengthwhich differs from the first wavelength by at least 50 nm. There canalso be a third layer, where the difference in optical path length is atleast 0.1 wavelength with respect to a light of a third wavelength,where the third wavelength is at least 50 nm different than both thefirst and second wavelengths. For example, the first layer can be withrespect to green light, the second layer with respect to red light, andthe third layer with respect to blue light.

In the multiple layer version of the invention, the first layer canfocus light at a first focal spot. The second layer can focus light at asecond focal spot, spaced apart from the first focal spot, andadditional layers can focus light at further additional spots.

Typically the material for the lens comprises a polymeric matrix.Optionally an absorber, preferably in an amount of at least 0.01% byweight of the material, can be used where the absorber is for light ofthe laser beam wavelength.

The system also includes apparatus for modifying the optical propertiesof a polymeric disc to form the lens. The apparatus can comprise a laseremitting a pulsed beam, a modulator for controlling the pulse rate ofthe beam, focusing lens for focusing the beam into a first region in thedisc, and a scanner for distributing the focused beam into multiple lociin the region. There is also a holder for the lens, and means for movingthe disc so that multiple regions of the disc can be modified.Preferably the modulator produces pulses between 50 and 100 MHzrepetition rate. The pulse emitted by the laser can have a duration offrom about 50 to about 100 femtoseconds and an energy level of about 0.2nJ. The focusing lens can be a microscope objective that focuses to aspot size of less than 5 μm.

The scanner can be a raster scanner or a flying spot scanner, and in thecase of a raster scanner, cover a field of view of about 500 μm.

The system also provides a method for forming these lenses. When forminga lens a disc formed of an optical material is held, and then modifiedloci are formed in the held disc with a laser beam.

The method can comprise the steps of emitting a pulsed beam from thelaser, controlling the pulse rate of the beam with the modulator,focusing the beam in a first region in the lens, distributing thefocused beam in multiple loci in the region, and moving the lens tomodify loci in multiple regions of the disc.

The method and system can also be used for modifying the opticalproperties of a lens, such as an intraocular lens located in theposterior chamber or anterior chamber, contact lens, or natural lens.This can be affected by forming modified loci in the lens just as ifthey have been using the same procedure for forming a modifying lensthat is used before the lens is implanted. One difference is that thelens in situ is not moved to modify different regions, but rather thefocusing system of the apparatus is used to illuminate different regionsof the in situ lens. During in situ processing, the eye of the patientcan be stabilized according to conventional techniques used duringophthalmic surgery.

DRAWINGS

These and other features, aspects, and advantages of the presentinvention will become better understood with regard to the followingdescription, appended claims, and accompanying drawings where:

FIG. 1A is a front elevation view of an intraocular lens having featuresof the present invention;

FIG. 1B is a top plan view of the lens of FIG. 1A;

FIG. 2 schematically shows a portion of the body of an intraocular lenshaving two layers of modified loci;

FIG. 3 schematically shows a lens body having multiple layers ofmodified loci, where some of the layers are formed after placement ofthe lens in an eye;

FIG. 4A is a schematic view of one layer of the lens of FIG. 1 modifiedto generate a spherical focusing effect;

FIG. 4B is a top plan view of the layer shown in FIG. 4A;

FIG. 4C is a schematic view of a layer of the lens of FIG. 1 modified togenerate an aspherical focusing effect;

FIG. 4D is a schematic view of a layer of the lens of FIG. 1 providing adefocusing meridian to accommodate for astigmatism;

FIG. 4E is a schematic top plan view of the layer of the lens of FIG. 4Dat the horizontal meridian;

FIGS. 5 and 6 schematically show the principles utilized for forming themodified loci;

FIG. 7 schematically shows the layout of an apparatus according to thepresent invention for forming the aforementioned lenses;

FIG. 8 shows a flow chart for an algorithm useful in the apparatus ofFIG. 7;

FIG. 9 graphically shows the effect of including a UV absorber inmaterial used for forming a lens;

FIG. 10A graphically shows the relationship between the change of theindex of refraction of modified loci as a function of laser pulseenergy;

FIG. 10B graphically shows the relationship between the change inrefractive index of a modified lens as a function of the number of laserbeam pulses at a fixed pulse energy;

FIG. 11 schematically represents forming a lens according to the presentinvention using a layered raster-scan method;

FIG. 12 schematically represents forming a lens according to the presentinvention using a layered flying spot scanning method;

FIG. 13 schematically shows a process for creating a refractive layerstructure by point wise variation of a change in refractive index; and

FIG. 14 schematically shows how a natural lens can be modified in situ.

DESCRIPTION Overview

In accordance with the present invention, a customized intraocular lens,referred to as a Customized Intraocular Phase Shifting Membrane(C-IPSM), is manufactured using a laser unit that generates a pulsedlaser beam. More specifically, a laser unit optionally can generatelaser beam pulses at 50 MHz, with each pulse having duration of about100 femtoseconds and an energy level of about 0.2 to about onenanojoule. As envisioned for the present invention, the focal spot ofthe laser beam is moved over a surface of plastic material having arefractive index “n_(o)”. This alters a sub-surface layer by creating apattern of changes in the refractive index of the material (Δn).

Preferably, the customized intraocular lens (C-IPSM) is fabricated froma flat sheet of plastic that has a first side and a second side, and athickness of from about 50 to about 400 mm between the two sides. Duringthe manufacture of the customized intraocular lens (C-IPSM), the laserunit alters a sub-surface layer having a depth of only about 50 microns.The purpose of the layer of altered material in the layer is tocompensate for optical aberrations of the patient to receive the C-IPSM.Specifically, this compensates for optical aberrations introduced into alight beam by an optical system (e.g., an eye).

The pattern of refractive index changes created in the plastic sheetresults from exposing the plastic material to the electronic disruptionand heat created by the layer in a predetermined manner. In particular,this change in refractive index is accomplished by sequentially focusinga laser beam onto a plethora of contiguous loci in the material. Theresult at each locus is an Optical Path Difference (OPD) for lightpassing through the spot. For a given material (e.g., plastic), having agiven change in refractive index (Δn) (e.g., Δn=0.01), and for a givendistance through the material (e.g., 5 microns), an OPD (i.e., phasechange) for light of a wavelength (λ) can be established. In particular,an OPD of λ/10 can be established for each 5 microns of locus depth.Thus, depending on the required refraction for each spot, the spot depthwill be between 5 and 50 microns.

The amount of change in refractive index (Δn) can be altered fordifferent locus positions, e.g., between a lowest value of Δn=0.001 to ahighest value of Δn=0.01. Thus, depending on the required refraction, avalue between Δn=0.001 and Δn=0.01 can be used, exploiting a modulo 2πphase wrapping technique.

Each locus can be created with the laser unit using a predeterminednumber of laser bursts (i.e., an “i” number of bursts). Preferably, eachburst includes approximately 50 pulses and is approximately 1microsecond in duration. During each burst, an alteration of asubstantially cylindrical volume of material occurs through a depth ofapproximately five microns with a diameter of about one micron. Thus alocus contains at least one site, and typically up to 10 sites. Ingeneral, each burst causes an OPD of about one-tenth of a wavelength(λ/10). For “i” bursts: OPD=i(x(λ/10)). Preferably, for the presentinvention there is approximately a λ/10 change for every 5 microns oflocus depth (i.e., “i” is in a range of 1 to 10). For example, considera situation wherein it is desired to create an OPD of 0.3λ. In this casethe laser unit is focused for an initial burst at a depth of twentymicrons (i.e., i=3). Thereafter, the laser unit is refocused onto thelocus two more times, with the focal point of the laser beam beingwithdrawn each time through a distance of five microns for eachsubsequent burst. The number “i” is selected depending on the amount ofrefraction that is desired at the locus (e.g., 0.2λ for i=2; and 0.7λfor i=7). A locus can be created by advancing, rather than withdrawing,the focal point of the laser beam.

In accordance with another version of the invention, employingvariations of Δn, each locus is created with the laser unit using avarying number of pulses per laser burst. Each laser burst creates asite, there being from 1 to 10 sites per locus. Preferably, each burstincludes between 5 pulses and 50 pulses and is approximately 100nanoseconds to 1 microsecond in duration. During each burst, analteration of a substantially cylindrical volume of material occursthrough a depth of approximately five microns with a diameter of aboutone micron. In general, as mentioned above, each burst causes an OPD ofabout one-hundreds of a wavelength (λ/100) to one-tenth of a wavelength(λ/10). Thus, by maintaining a certain number of pulses per burst perspot, for example 5 pulses, on each subsequent location for oneparticular spot, a predetermined OPD, in this example one-tenth of awavelength (λ/10), resulting from (10×(λ/100)), is obtained. Variationsin OPD are incurred via the change in Δn from locus to locus, as thefemtosecond laser beam is moved in a transverse direction, i.e.,parallel to the surface of the plastic membrane.

Once the refractive properties desired for the customized intraocularlens (C-IPSM) are determined, a template of the anterior surface layerof the intraocular lens is calculated. This information is then sent toa manufacturing station and used for programming the individual pixelsof the layers of the intraocular lens. Subsequently, after implantationof this customized intraocular lens, incoming light is refracted by theoptical components in the pseudophakic eye to form an improved image onthe retina of the eye.

The refraction of an incoming beam by the customized intraocular lens(C-IPSM) makes the optical path lengths of individual beams in anyincoming beam appear to be substantially equal to each other. In thisway, an incoming beam which carries the image information, iscompensated by the customized intraocular lens (C-IPSM) to account forthe refractive aberrations of the pseudophakic eye that are evidenced bythe appropriate measurement data.

With regard to the optical performance of the micro-structured surfacelayer of the customized intraocular lens (C-IPSM), several refractiveand diffractive optical principles can be employed for differentmodifications of the performance of the customized intraocular lens(C—IPSM). The designs comprise refractive, with or without phasewrapping, and diffractive phase (“GRIN”) structures. Spherical,aspherical, achromatic, bifocal and multifocal embodiments are possible.

Lenses

Lenses having features of the present invention can be of any type oflens implanted in the eye, including contact lenses, intraocular lensesplaced in the anterior or posterior chamber, and corneal lenses. IOLsplaced in the posterior chamber often can be phakic when the naturalcrystalline lens is present and pseudophakic where the naturalcrystalline lens has been removed such as by cataract surgery. Theinvention is also useful for modifying lenses in situ, including lensessuch as contact lenses in the anterior chamber, IOLs in the posteriorchamber or anterior chamber, the natural cornea and natural crystallinelenses.

With regard to FIGS. 1A and 1B, an intraocular lens 10 having featuresof the present invention comprises a central disc shaped body 12 havingan anterior surface 14 and a posterior surface 16. Preferably both theanterior surface 14 and posterior surface 16 are substantially planar,i.e., they have little or no curvature such as concave or convexcurvature. Use of the techniques of the present invention allows aplano-plano intraocular lens to be formed. As is conventional with manyintraocular lenses, there can be a pair of haptics 18 for holding thelens in the posterior chamber

The terms “anterior” and “posterior” refer to surfaces of a lens as itis normally placed in the human eye, with the anterior surface 14 facingoutwardly, and the posterior surface 16 facing inwardly toward theretina. The lens 10 has an optical axis 19, which is an imaginary linethat defines the path along which light propagates through the lens 10.In a version of the invention shown in FIGS. 1A and 1B, the optical axis19 is coincident with the lens's mechanical axis, but this is notrequired.

Although it is preferred that all of the optical effects of the lens beprovided by modified locus in the body 12, as described below, it ispossible that corrective optical effects can also be provided in theconventional way, such as by having the anterior surface, the posteriorsurface, or both curved, such as convex, concave, or complex curvature.It is not necessary that all optical corrections be provided by modifiedloci according to the present invention, although that is the preferred.

A lens having features of the present invention can be used forcorrecting vision errors, such as for myopia (near-sighted), hyperopia(far-sighted), and astigmatism. The lens can be aspheric and/or toric.

The body 12 of the lens 10 is made of an optical material, which is anymaterial presently existing or existing in the future that is suitablefor making a lens for implantation in an eye. Typically the material ispolymeric. The material used for the body 12 shows a change ofrefractive index when treated with a laser, as described in detailbelow.

Non-limiting examples of such materials include those used in themanufacture of ophthalmic devices, such as contact lenses and IOLs. Forexample, the present invention can be applied to siloxy-containingpolymers, acrylic polymers, other hydrophilic or hydrophobic polymers,copolymers thereof, and mixtures thereof.

Non-limiting example of siloxy-containing polymers that can be used asoptical materials are described in U.S. Pat. Nos. 6,762,271; 6,770,728;6,777,522; 6,849,671; 6,858,218; 6,881,809; 6,908,978; 6,951,914;7,005,494; 7,022,749; 7,033,391; and 7,037,954.

Non-limiting examples of hydrophilic polymers include polymerscomprising units of N-vinylpyrrolidone, 2-hydroxyethyl methacrylate,N,N-dimethylacrylamide, methacrylic acid, poly(ethylene glycolmonomethacrylate), 1,4-butanediol monovinyl ether, 2-aminoethyl vinylether, di(ethylene glycol)monovinyl ether, ethylene glycol butyl vinylether, ethylene glycol monovinyl ether, glycidyl vinyl ether, glycerylvinyl ether, vinyl carbonate, and vinyl carbamate.

Non-limiting examples of hydrophobic polymers include polymerscomprising units of C₁-C₁₀ alkyl methacrylates (e.g., methylmethacrylate, ethyl methacrylate, propyl methacrylate, butylmethacrylate, octyl methacrylate, or 2-ethylhexyl methacrylate;preferably, methyl methacrylate to control mechanical properties),C₁-C₁₀ alkyl acrylates (e.g., methyl acrylate, ethyl acrylate, propylacrylate, or hexyl acrylate; preferably, butyl acrylate to controlmechanical properties), C₆-C₄₀ arylalkyl acrylates (e.g., 2-phenylethylacrylate, benzyl acrylate, 3-phenylpropyl acrylate, 4-phenylbutylacrylate, 5-phenylpentyl acrylate, 8-phenyloctyl acrylate, or2-phenylethoxy acrylae; preferably, 2-phenylethyl acrylate to increaserefractive index), and C₆-C₄₀ arylalkyl methacrylates (e.g.,2-phenylethyl methacrylate, 3-phenylpropyl methacrylate, 4-phenylbutylmethacrylate, 5-phenylpentyl methacrylate, 8-phenyloctyl methacrylate,2-phenoxyethyl methacrylate, 3,3-diphenylpropyl methacrylate,2-(1-naphthylethyl)methactylate, benzyl methacrylate, or2-(2-naphthylethyl)methacrylate; preferably, 2-phenylethyl methacrylateto increase refractive index).

A preferred material is a hydrophobic acrylic polymer made fromN-benzyl-N-isopropylacrylamide, ethyl methacrylate, and butyl acrylatecross linked by ethylene glycol dimethacrylate.

The material can optionally contain a ultraviolet light blocker, such asacrylic derivatives of benzotriozoles.

For a typical IOL, the body 12 has a diameter of about 6 mm andpreferably has a thickness 20 of from about 50 μm to about 400 μm, andmost preferably about 250 μm. This is a smaller thickness than withconventional IOLs. When the lens 10 is folded to be placed in theposterior chamber, because of its relative thinness, it is possible fora surgeon to make a smaller incision than with conventional lenses. Thiscan increase safety for the patient, and it is believed can result inreduced post-operative recovery time, and reduced surgically inducedastigmatism. Also in the version of the invention where the anterior andposterior surfaces are planar, it is easy to insert the lens, therebyrendering some instances of cataract surgery less traumatic.

The optical effect provided by the lens 10 is a result of the presenceof modified loci in the body 12, where the modified loci having beenformed by a laser beam that causes the modified loci to have a differentrefractive index than the lens material before modification.

FIG. 2 shows a portion of an exemplary lens body 12 having two spacedapart planar layers generally parallel to the anterior surface 14 of thelens body 12, an upper layer 22 and a lower layer 23. Layers 22 and 23are preferably 50 μm in thickness. Only a portion of each layer isshown, and exemplary modified loci are shown only for the upper layer22. Layer 22 contains exemplary contiguous modified loci 24 a-24 j. Eachlocus 24 is cylindrical shape with a diameter of about 1 μm with itsaxis generally parallel to the optical axis 19 of the lens. Each locus24 a-j contains one or more sites 26 formed by a single pulse from alaser. Each site is typically about 5 μm in height, and thus themodified loci range in height from about 5 to about 50 μm. As shown inFIG. 2, locus 24 a contains 10 sites 26, locus 24 b contains 9 sites,continuing to locus 24 j which contains one site.

The change in refractive index of the material present in the modifiedloci results in a change in the optical path length. In particular, theoptical path length of each modified locus is increased by about 0.1wave as compared to the optical path length of a non-modified locus,with respect to light of a selected wavelength. Generally green lighthaving a wavelength of about 555 nm is the basis for modification sincethe light of that wavelength is typically optimally received by thehuman eye. Thus each modified locus has an optical path length of about0.1 to about 1 wave greater than the optical path length of anon-modified locus, wherein the wavelength is with respect to light ofwavelength of 555 nm.

Preferably there are sufficient modified loci that at least 90%, andmore preferably at least 99%, of the light projected onto the anteriorsurface 14 of the lens 10 in a direction generally parallel to theoptical axis 19 passes through at least one modified locus 24.

FIG. 3 shows a schematic view of the multilayered, micro-structuredcustomized intraocular lens 10 that is membrane-shaped, exhibiting adisc-like planar appearance, with a diameter 62 of about 6 mm and awidth 64 of about 500 μm. The refractive properties of themicro-structured customized intraocular lens are inscribed in thinlayers, indicated as 66 to 88, which are typically 50 μm thick.Initially, a posterior layer, e.g., between the posterior surface 16 andplane 69, at depth 65, is generated. The layers 72, 74, 76, 78, 80, 82,84, 86 and 88 are micro-structured accordingly. Additional layers 66, 68and 70 can be micro-structured during an in-vivo fine-tuning procedureof the refractive properties of the implanted customized intraocularlens, covering the anterior portion of the intraocular phase-shiftingmembrane between planes 69 and 71, having a thickness 67.

Each layer 66-88 contains modified loci, and typically more than1,000,000 modified loci, and up to about 30,000,000 loci, and each layertypically is in a plane substantially parallel to the anterior surface14 of the lens body 14.

FIG. 4 shows pattern of modified loci used for achieving differentoptical effects. The layer shown in FIGS. 4A and 4B provide a sphericaladjustment in the amount of about +0.4 diopter. It comprises threeannular rings, 402, 404, and 406 concentric with the optical axis 19 andsurrounding a central region 408. Thus the modified loci are in acircular pattern concentric with the optical axis. The outer edge of theoutermost radius ring 402 is at r₄, which is 3 mm from the optical axis19, i.e., it is at the peripheral edge of the body 12. The outside edgeof the second ring 404, r₃, is 2.5 mm from the optical axis 19. Theoutside edge of the third ring 406, is at r₂ which is 2 mm from theoptical axis 19. The central portion 408 outside edge r₁ is at 1.4 mm.Each ring is made of plurality of contiguous modified loci wherein thenumber of sites in each locus increases as the locus is closer is to theoptical axis 19. Thus the modified loci at the outer edge of the firstring 402 has one site, and thus a height of about 5 μm, while themodified locus closest to the optical axis 19 has 10 sites, and thus isabout 50 μm in height.

The layer shown in FIG. 4C is patterned to provide an asphericalfocusing effect. In this layer, the inner most ring 406′ and the centralregion 408′ have the same pattern as the ring 406 and the central region408, respectively, in FIG. 4A. However, the outer rings 402′ and 404′have the modified loci reversed in that there are more sites in themodified loci farther from the optical axis 19 than there are formodified loci radially inwardly. Because r₁, r₂, and r₃ are the same inthe version shown in FIG. 4C as in 4A, the top plan schematic view of 4Bis also applicable to the layout shown in FIG. 4C.

FIG. 4D shows a pattern for the modified loci to accommodate forastigmatism and/or toricity taken at the horizontal meridian of thelens. In this version, all the rings 402″, 404″, and 406″, and thecentral region 408″ decrease in height the closer the modified loci inany single ring is closer to the optical axis 19, exhibiting adefocusing effect in the horizontal meridian.

The top planar view of the layer of FIG. 4D is shown in FIG. 4E whereinthe layer shown in FIG. 4D is positioned horizontally. The verticalmeridian of the astigmatic connecting layer of FIG. 4D is the same asshown in FIG. 4A. The horizontal meridian provides −0.4 diopter powerand the vertical meridian provides +0.4 diopter power. At the 45°diagonals, there is no refraction effect.

There are smooth transitions between the various regions of the layerdepicted. Each locus has a very small diameter, on the order of about 1μm. The transition from the outside of a ring to the inside of a ringneed not be a steady step wise decrease in the number of sites becausethere can be multiple modified loci having the same number of sitesadjacent to each other.

The optical effect provided by the lens 10 can be easily increased ordecreased by changing the number of rings. For example, with the lensschematically shown in FIG. 4A, each ring provides a 0.1 dioptic power,and thus the lens shown in FIG. 4A provides 0.4 dioptic power. To make alens having a 10 dioptic power, where each ring contributes 0.1 diopter,the lens is made with about 100 rings, where 99 of the rings have thesame general configuration of rings 402, 404, and 406 in FIG. 4A, andthe center ring has the configuration of the center ring 408 shown inFIG. 4A. However, since there are more rings in the same surface area,each ring has a much smaller width than the rings in FIG. 4A.

FIGS. 5 and 6 demonstrate the principle of a modulo-2π phase wrappingtechnique that can be used to characterize the present invention.Specifically, the formed microstructure is generated to compensate foroptical path length differences within an array of neighboring rays,e.g., rays 542, 544 and 546, such that all of the contiguous individuallight beams 542, 544 and 546 are in phase with each other. For thediscussion here, the individual contiguous light beams 542, 544 and 546are considered exemplary.

In FIG. 5, the sinusoidal characteristic of a first light beam 542 andsecond light beam 544 are shown as a function of time. If the lightbeams 542 and 544 were in phase with each other, which they are not inFIG. 5, the second light beam 544 would be shown superimposed on top ofthe first light beam 542. As shown, however, the light beams 542 and 544are out-of-phase relative to each other, and this difference in phase isshown as a phase shift 590. Conceptually, the phase shift 590 can bethought of as either a difference in time or a difference in distancetraveled. For instance, at the specific point in time 592, the firstlight beam 542 is at a certain position in free space. Due to the phaseshift 590, however, the second light beam 544 is not at this sameposition until the subsequent point in time 594. For the situation shownin FIG. 5, and when considering that the first light beam 542 will gothrough a complete period, or cycle, of 360° (2π radians) as it travelsfrom the point in time 592 to a point in time 596, that the magnitude ofthe phase shift 590 between the first light beam 542 and the secondlight beam 544 is less than 2π.

With regard to the first light beam 542 and a third light beam 546depicted in FIG. 6, the point in time 592 for first light beam 542corresponds to the point in time 598 for the third light beam 546. Thus,the total phase shift 604 which exists between the first light beam 542and the third light beam 546 is more than 2π. As contemplated, for thepresent invention, the total phase shift 604 actually includes a modularphase shift 500 which is equal to 2π, and an individual phase shift 502which is less than 2π. Using this notation, the total phase shift 604between any two light beams can be expressed as the sum of a modularphase shift 500 which is equal to n2π, where “n” is an integer, and anindividual phase shift 502, the so-called modulo 2π phase shift, whichis less than 2π. Thus, the integer “n” may take on different values(e.g., 0, 1, 2, 3, . . . ) and, specifically, for the light beam 544(FIG. 3A) n=0, while for the light beam 546 (FIG. 3B) n=1. In all cases,the total phase shift 604 for each light beam 544, 546, is determined bycomparing it with the corresponding light beam 542 as a reference. Themodular phase shift 500 can then be subtracted from the total phaseshift 604 to obtain the individual phase shift 502 for the particularlight beam 544, 546. First, however, the total phase shift 604 isdetermined.

Referring to FIG. 4A, at each locus the modular phase shift 500 (=n×2π)is subtracted from the total phase shift 604, to yield the individualphase shift 502, e.g., in FIG. 4A, the modular phase shift 500 amountsto 0×2π=0 in the center zone, 1×2π in the second zone (r₁ to r₂),2×2π=4π in the third zone (r₂ to r₃) and 3×2π=6π in the fourth zone (r₃to r₄). The individual phase shifts 502 (0 to 2π, corresponding to 0.0to 1.0 waves), are inscribed into the loci, amounting to 5 μm to 50 μmdepth.

Thus, with further reference to FIG. 4A the local phase-shift independence of the distance from the pupillary axis is plotted, asimposed by the micro-structured customized intraocular lens, changingfrom a phase-shift of 2π, equivalent to 1.0 waves, at the optical axis19 is to zero at the radial position r₁. It is assumed, that the initialoptical beam, impinging on a micro-structured customized intraocularlens is collimated, exhibiting individual rays with identical opticalpath lengths, shaping a planar optical wave. As a result of the travelof the individual rays through the micro-structured customizedintraocular lens, a focused optical wave is generated. In the centerpart of the optical beam, inside an area limited by the radius r₁, theoptical phase shift changes quadratically with respect to the distancefrom the optical axis. At position r₁, a phase-shift of zero, equivalentto 0.0 waves, is implemented. The adjacent ray, laterally from radiusr₁, is subjected to a phase-shift of 2π, equivalent to 1.0 waves,resulting in the characteristic phase-jumps of 2π, equivalent to 1.0waves, at the zone boundaries of a modulo 2πphase wrapping technique.With regard to FIG. 5, such phase jumps by an amount of 2π, respectivelya multiple of 2π (“shift 500”) can be visualized as “catching the nextwave” which is delayed by one full cycle 2n, as related to the adjacentlight beam. In general, at each of the radial positions r₁, r₃, r₄, thelocal phase-shift jumps by 2π, corresponding to 1.0 waves, whereas inbetween these jumps the phase changes quadratically, from a value of 2πequivalent to 1.0 waves, to zero, equivalent of 0.0 waves.

Generally there are sufficient modified loci that the refractive indexof the body has been modified sufficiently to change the dioptic powerof the body by at least +0.5 (+0.5 to +X) or at least −0.5 (−0.5 to −Y)where X can be about 48 and Y can be about 15.

In the multilayer versions of the invention, typically the layers arespaced-apart by at least one micron, and preferably by at least 5 μm.

In the multilayer version, it is possible to optimize the various layersfor a particular selected wavelength of light. For example, a firstlayer can be optimized for the light of a first wavelength, such asgreen, the second layer for light of a second wavelength, which differsfrom the first wavelength by at least 50 nm, such as red light, and athird layer can be optimized for light of a third wavelength thatdiffers from both the first and second by at least 50 nm, such as bluelight.

Also different layers can be formed to focus light at different focalspots.

Another use of multi layers is to have a single layer perform multipleoptical corrections rather than have all vision corrections in a singlelayer. Thus it is possible to have a first layer provide a diopteradjustment, and other layers provide other optical corrections such as atoric adjustment or an aspheric adjustment. Thus the first layer canprovide a diopter adjustment, the second layer loci can provide a toricadjustment, and a third layer can provide an aspheric adjustment.

System for Making and Modifying Lenses

The present invention uses very short laser pulses of sufficient energytightly focused on an optical, polymeric material to form the lenses.High intensity of light at the focus point causes a nonlinear absorptionof photons (typically multi-photon absorption) and leads to a change inthe refractive index of the material at the focus point. The region ofthe material just outside the focal region is minimally affected by thelaser light. Accordingly, select regions of an optical, polymericmaterial are modified with a laser resulting in a positive change in therefractive index in these regions.

Thus lenses can be formed by irradiating select regions of an optical,polymeric material with a focused, visible or near-IR laser having apulse energy from 0.05 nJ to 1000 nJ. The irradiated regions exhibitlittle or no scattering loss, which means that the structures formed inthe irradiated regions are not clearly visible under appropriatemagnification without contrast enhancement.

The pulse energy of the focused laser used in the method in-part dependson the type of optical material that is being irradiated, how much of achange in refractive index is desired and the type of structures onewants to imprint within the material. The selected pulse energy alsodepends upon the scan rate at which the structures are written into theoptical material. Typically, greater pulse energies are needed forgreater scan rates. For example, some materials call for a pulse energyfrom 0.2 nJ to 100 nJ, whereas other optical materials call for a pulseenergy from 0.5 nJ to 10 nJ.

The pulse width is preserved so that the pulse peak power is strongenough to exceed the nonlinear absorption threshold of the opticalmaterial. However, the glass of a focusing objective used cansignificantly increase the pulse width due to the positive dispersion ofthe glass. A compensation scheme is used to provide a correspondingnegative dispersion that can compensate for the positive dispersionintroduced by the focusing objective(s). Accordingly, the term “focused”in this application refers to the focusing of light from a laser withinan optical, polymeric material using a compensation scheme to correctfor the positive dispersion introduced by the focusing objective(s). Thecompensation scheme can include an optical arrangement selected from thegroup consisting of at least two prisms and at least one mirror, atleast two diffraction gratings, a chirped mirror and dispersioncompensating mirrors to compensate for the positive dispersionintroduced by the focus objective

The use of the compensation scheme with the focusing objective cangenerate pulses with pulse energy from 0.01 nJ to 100 nJ, or from 0.01nJ to 50 nJ, and a pulse width of from 4 fs to 200 fs. At times, it canbe advantageous to generate a laser pulse with energies from 0.2 nJ to20 nJ, and a pulse width of from 4 fs to 100 fs. Alternatively, it canbe advantageous to generate a laser pulse with energies from 0.2 nJ to10 nJ and a pulse width of from 5 fs to 50 fs.

The laser can generate light with a wavelength in the range from violetto near-infrared radiation. In various embodiments, the wavelength ofthe laser is in the range from 400 nm to 1500 nm, from 400 nm to 1200 nmor from 600 nm to 900 nm.

FIG. 7 schematically shows a preferred apparatus 702 for formingmodified loci. The apparatus 702 comprises a laser 704, preferably afemtosecond laser as used in 2-photon microscopes, a control unit 706, ascanning unit 708, a holder 710 for the lens disc 12, and means 712 formoving the disc 12 in which modified loci are being formed. A suitablelaser is available from Calmar Laser, Inc, Sunnyvale, Calif. Each pulseemitted by the laser can have a duration of from about 50 to about 100femtoseconds and an energy level of at least about 0.2 nJ. Preferablythe laser 704 generates about 50 million pulses per second at awavelength of 780 nm, a pulse length of about 50 fs, each pulse having apulse energy of about 10 nJ, the laser being a 500 mW laser. An emittedlaser beam 721 is directed by a turning mirror 722 through anacustooptic modulator 724 that controls the frequency of the pulses,typically at about 50 MHz to 100 MHz repetition rate. The laser beam 721typically has a diameter of 2 mm when emitted by the laser. The laserbeam 721 then travels through the scanning unit 708 that spatiallydistributes the pulses into a manifold of beams. The pattern can be araster-scan pattern or flying spot pattern. The scanning unit 708 iscontrolled by a computer control system 726 to provide the desiredconfiguration of the modified loci in the disc 12.

The beam 721 emitted from the laser has a diameter from about 2 to about2.5 nm. The beam 721, after exiting the scanner 708, is then focused toa size suitable for forming modified loci, typically forming loci havinga diameter from about 1 to about 3 μm. The focusing can be effected witha telescopic lens pair 742 and 744, and a microscopic objective 746,where another turning mirror 748 directs the beam from the lens pair tothe microscopic objective. The focusing microscope objective can be a40×/0.8 objective with a working distance of 3.3 mm. The scanning andcontrol unit are preferably a Heidelberg Spectralis HRA scanning unitavailable from Heidelberg Engineering located in Heidelberg, Germany.

The optics in the scanning unit allow a region having a diameter ofabout 150 to about 450 μm to be modified without having to move eitherthe disc 14 or the optics. Typically, a single layer of 50 μm thicknesscan be micro-structured in a region in about one minute.

To modify other regions of the disc 12 it is necessary to move theholder 710 with the moving means 712. The moving means 712 allowsmovement in the “z” direction for providing modified loci in differentlayers, and also in the “x” and “y” directions for treating differentregions at the same depth. The moving means 712 serves as a precisepositioning system to cover the full diameter of an intraocular disk,which typically has a diameter of 6 mm.

The holder 710 can be a bracket, a conveyor belt with recesses sized forthe lens, a tray having recesses for the lens, and any other structurethat can hold the lens sufficiently stable for formation of a desiredrefraction pattern.

The moving means can be any mechanical structure, typically driven bymotors, that provide movement in the x, y and z directions, i.e., threedimensional movement. The motors can be stepper motors. Typicallymovement is up to about 10 mm/second.

The lens manufacturing procedure uses stepping via xyz-positioning fromone scan-field (typically 450 μm diameter) to the next scan-field of the2-photon microscope (raster-scan or flying spot scan). The 2-photonmicroscope provides the depth-scan. Typically, one refractive layer canbe completed within the range of the 2-photon microscope. Alternatively,the z-positioning is provided by mechanical z-positioning, in order toprovide extended reach to deeper layers in disc 14.

The control unit 706 can be any computer that includes storage memory, aprocessor, a display, and input means such as a mouse, and/or keyboard.The control unit is programmed to provide the desired pattern of themodified loci in the disc 12 by providing control instructions to thescanning unit 708, and when necessary to the moving means 712.

An exemplary program for forming a disc is shown in FIG. 8, where thebeam is maintained stationary (i.e., the scanner is not used) and thetarget disc is moved mechanically. When the program commences, the useris prompted to select the desired lens in step 801. Next, the userprovides the desired speed for scanning the disc 14 during the laserpulsing in step 802. Only when the computer determines this speed is asafe speed, typically 4 mm or less of travel per second, does theprogram accept the input in step 803. The program next sets the laser touse maximal power, and prompts the user for confirmation to continue instep 804. At this stage the program provides the user a last opportunityto avoid lens writing before in step 805. If the user has chosen toabort writing, the program terminates. Otherwise, the program modifies alog file in step 806 to record variables appropriate to record keepingand advances.

The laser begins in a position at one extreme in both the x and ydirections, which constitutes the home position. Each layer in amodified lens can be thought of as a stack of minilayers of a depthequal to the thickness of a site. On a given minilayer, the laseradvances across one dimension (e.g., x), while holding the other two(e.g., y and z) constant, thereby writing a series of sites. The programbegins each series by finding a grid location that constitutes thestarting point of the current series in step 807. Next, the programwrites that series wherever appropriate in step 808. When the programhas scanned the laser to the outer extent of a given series, it amendsthe log file to reflect that the series is complete in step 809. Theprogram then queries the input instructions to determine if there aresubsequent series to be formed in step 810. This process continues untilall series of modified loci in a given minilayer are formed. Whenever anew series needs to be prepared, the program advances the secondvariable (e.g. y), and resets the first dimension (e.g. x) to begin anew series 807. Once the laser has finished scanning across all gridlocations of the minilayer, having considered each successively andhaving written the series when appropriate, the program is done withwriting for that minilayer. The scanner then resets the first and seconddimensions to their original positions in step 811, thereby returningthe laser to its home position. The program updates the log file to showthat the layer is complete in step 812.

The program then queries to determine if more minilayers are necessaryin step 813 to achieve the user's desired lens. If more minilayers areneeded, the program advances the third dimension (e.g., z) and repeatsthe above process, beginning with finding the first grid location forthe first line of the new layer 817. If no more minilayers arenecessary, the program returns the laser to its original, home positionfor all three dimensions in step 814, modifies the log file to reflectboth that writing is complete and the system time in step 815, andterminates execution. Once a layer, which typically has from 1 to 10minilayers is completed, then any additional layer that needspreparation can be prepared using the same process. In an optionalprogram, the focus point of the scanner 708 can be moved in the zdirection (depth) to form deeper sites. Generally all sites at the samedepth are formed, and then all sites at the next depth within a layerare formed, until all the sites in a layer are completed.

The storage memory can be one or more devices for storing data,including read-only memory (ROM), random access memory (RAM), magneticdisk storage mediums, optical storage mediums, flash memory devices,and/or other machine-readable mediums for storing information.

The control can be implemented by hardware, software, firmware,middleware, microcode, or a combination thereof. When implemented insoftware, firmware, middleware or microcode, the program code or codesegments to perform the necessary tasks can be stored in amachine-readable medium such as a storage medium or other storage(s). Aprocessor may perform the necessary tasks. A code segment may representa procedure, a function, a subprogram, a program, a routine, asubroutine, a module, a software package, a class, or a combination ofinstructions, data structures, or program statements. A code segment maybe coupled to another code segment or a hardware circuit by passingand/or receiving information, data, arguments, parameters, or memorycontents. Information, arguments, parameters, data, etc. may be passed,forwarded, or transmitted through a suitable means including memorysharing, message passing, token passing, network transmission, etc.

Optionally an adaptive-optics module (AO-module) can be used to simulatethe effect of a refractive correction, with regard to image clarity anddepth of focus. The AO-module can be composed of a phase-pointcompensator and an active mirror for the purpose of pre-compensatingindividual light beams generated by the laser 704. An adapted opticsdevice to compensate for asymmetric aberrations in a beam of light isuseful for the invention described in my U.S. Pat. No. 7,611,244. Amethod and apparatus for pre-compensating the refractive properties ofthe human with an adaptive optical feedback control is described in myU.S. Pat. No. 6,155,684. Use of active mirrors is described in my U.S.Pat. No. 6,220,707.

The optical resolution (Δxy, Δz) for a two-photon signal amounts to:2Δxy=2×(0.325λ)/(NA0.91)=622 nm (1/e² diameter),Δz=2×0.532λ×1/(n−√n²−NA²)=3102 nm (NA=Numerical Aperture, e.g., 0.8).This yields a site size.

Typical scan-fields in the raster scan mode amount to: 150 μm field ofview: 1536×1536 pixels at 5 Hz or 786×786 pixels at 10 Hz; 300 μm fieldof view: 1536×1536 pixels at 5 Hz or 786.times.786 pixels at 9 Hz; 450μm field of view: 1536×1536 pixels at 5 Hz or 786×786 pixels at 9 Hz.

For quality control while forming the modified loci, the laser can beused to generate light from autofluorescence of the material of thelens. Modified loci generate more fluorescence than non-modifiedmaterial. If a suitable increase in emitted fluorescence light is notdetected, that indicates that the process for forming the modified lociis not proceeding properly. A suitable system for detectingautofluorescence is shown in FIG. 7 of my copending U.S. patentapplication Ser. No. 12/717,866 filed even date herewith, entitled“System for Characterizing A Cornea And Obtaining An Ophthalmic Lens”.Also, the autofluorescence detected can be used for positioning thefocal point of the system of the laser beam from the microscopeobjective 746 for forming additional loci, using detected modified locihas a reference position.

The optical effects provided by the lens 10 for any particular patientcan be determined using conventional techniques for designing a lens.See for example the techniques described in U.S. Pat. No. 5,050,981(Roffman); U.S. Pat. No. 5,589,982 (Faklis); U.S. Pat. No. 6,626,535(Altman); U.S. Pat. No. 6,413,276 (Werblin); U.S. Pat. No. 6,511,180(Guirao et al); and U.S. Pat. No. 7,241,311 (Norrby et al). A suitabletechnique is also described in my aforementioned copending U.S. patentapplication Ser. No. 12/717,866.

Optionally an absorber for light of the laser beam wavelength can beincluded in the disc to reduce the amount of energy required for formingthe modified loci. It is desirable to have as little energy as possibleused for this purpose, because exposure to excess energy can result in acracking or other undesirable mechanical changes in the body 12.Exemplary of UV absorbers that can be used with the laser 704 arederivatives of benzotriozoles, such as2-(5-chloro-2-H-benzotriazol-2-yl)-6-(1,1-dimethyl-ethyl)-4-(propyenyloxy-propyl)phenol,and benzophenol derivatives, such as 3-vinyl-4-phenylazophenylamine,which is a yellow dye that absorbs at a wavelength of 390 nm. Preferablythe amount of UV absorber provided is at least 0.01% by weight, and upto about 1% by weight of the material used for forming the lens body 12.

In FIG. 9, the threshold energy (I) (nJ) for achieving permanentstructural change in plastic material in dependence of concentration (%)of an aromatic UV-absorber is shown. The typical characteristicdemonstrates a strong dependence of the threshold energy on theconcentration of the UV-absorber, indicating the enhancement of thelocal permanent structural change with the concentration of theUV-absorber, due to the increased probability of two-photon absorptionprocesses at 390 nm wavelength, half the wavelength of the referencedincident femtosecond laser pulses of 780 nm. The local interaction ofthe molecules of the plastic host results in a localized, partialmicro-crystallization of the plastic material, yielding an increase Δnof the refractive index n. At a concentration of 0.8% of theUV-absorber, as used in commercial intraocular lens materials, athreshold energy of about 0.1 nJ is required. In contrast, in undoped,bulk plastic material, a threshold energy of about 1 nJ is necessary.The stated threshold energies are based on a spotsize of about 1 μmdiameter, yielding threshold laser fluences of about 0.01 J/cm² and 0.1J/cm², respectively.

FIG. 10 shows the laser-material interaction process for changing therefractive index of a plastic material with femtosecond laser pulses. InFIG. 10A, the change Δn of the refractive index is plotted as functionof the pulse energy; in FIG. 10B, the change Δn of the refractive indexis plotted as a function of the number of pulses in the focal area at afixed pulse energy (e.g., 0.2 nJ). The curve 1050 in FIG. 10Ademonstrates that with increasing pulse energy from 0.1 nJ to 8 nJ, thechange Δn of the refractive index n is enhanced from approximately 0.1%to approximately 1.0%. The threshold for the initial occurrence of ameasurable change Δn of the refractive index n is denoted at position1052 of the curve 1050; at a pulse energy level of approximately 8 nJ,corresponding to a laser flux of approximately 0.8 J/cm.sup.2, thethreshold for photo disruption of the plastic material is reached,resulting in collateral damage of the material and opacifications,facilitating undesirable scattering losses of the light that istransmitted through the plastic material. As can be seen from curve1050, the range of possible pulse laser energies extends over two ordersof magnitude, from 0.05 nJ to 8 nJ, allowing for a safe operation of themanufacturing process which occurs at the lower end of the range, at apulse energy of approximately 0.2 nJ. In undoped plastic material, thesafe range for a corresponding manufacturing process extends only overclose to one order of magnitude. In addition, the low pulse energies,which are facilitated by the incorporation of the UV-absorber, allow foran especially smooth modification of the material properties, providingan intraocular phase-shifting membrane with extremely low lightscattering losses. In FIG. 10B, the curve 1060 indicates that thecumulative effect of approximately 50 laser pulses in the focal volumeyields refractive index changes Δn of the order 1%, sufficient forachieving a optical path length difference (OPD=(Δn)×thickness) of 1.0waves in a plastic material layer of 50 μm thickness, choosing a lowpulse energy of 0.2πJ.

In FIG. 11, the manufacturing process of an intraocular phase-shiftinglens where the scanning unit 708 provides a raster-scan pattern isexemplified. A procedure exhibiting the successive positioning of tenadjacent minilayers, each field comprising a densely spaced raster scanpattern is demonstrated. A stack 1170 of raster-scan minilayers 1176,1178, 1180, 1182, 1184, 1186, 1188, 1190, 1192, and 1194 is shown in anx-(1172) and y-(1174) coordinate system and extends over a thickness1202 of approximately 50 μm, i.e., each minilayer amounts toapproximately 5 μm. The lateral size of individual minilayers typicallyvaries between 150 μm to 450 μm for x (1198) and y (1199) dimensions,allowing for a change in the overlay of laser pulses in the focal volumeof 1 μm diameter per spot by a factor of ten. The surface 1996 is theend of a layer.

In FIG. 12, the manufacturing of an intraocular phase-shifting lenswhere the scanning unit 708 provides a layered flying spot pattern ispresented. As an example, the successive positioning of ten tightlyspaced circular scans is shown. A stack 1210 of circular scans 1216,1218, 1220, 1222, 1224, 1226, 1228, 1230, 1232, and 1234 is shown in a x(1212) and y (1214) coordinate system and extends over a thickness 1238of approximately 50 μm, i.e., the distance between individual circularscans or minilayers amounts to approximately 5 μm. The diameter 1236 ofthe circular scans can be from as small as a few microns toapproximately 450 μm, so that the amount of overlay of laser pulses perresolvable spot can be changed over a wide range. The speed of thesequence of spots per line can be chosen as required, by changing thelength of a scan line. Individual scan lines can exhibit various shapes.The resolution of the smallest scan details can comply with theresolution limit of the two-photon microscope of approximately 1 μmdiameter, whereas the raster scan procedure, as described with regard toFIG. 11, is limited to a resolution of approximately 150 μm, as given bythe smallest raster scan fields of a two-photon microscope. Forpractical applications, the manufacturing process of intraocularphase-shifting membrane is accomplished by the dual scan-system in acomplimentary fashion: The bulk part of the process is performed withthe time-optimal raster scan method, whereas the fine details of therequired refractive properties are contributed by the flying spotscanner with its inherent high spatial resolution.

In FIG. 13, the creation of a refractive layered structure by pointwisevariation of the refractive index change Δn is demonstrated. In general,the refractive structure is incorporated in a rectangularly shaped layerin the intraocular phase-shifting lens body 12. In FIG. 13, a portion ofthe intraocular phase-shifting membrane device is shown, comprised ofe.g., three neighboring stripes 1344, 1348, 1350, and 1384 with a widthof 150 μm, 300 μm and 450 μm, respectively. The overall dimensions ofthe region of body 14 amount to a width 1340 of 900 μm and a thickness1342 of 50 μm. Since the standard number of pixels per scan line in x-and y-directions is chosen as 1536×1536 pixels, the densities of pulsesper scan-line 1346, 1350, and 1354 amount to 10 pulses per micron, 5pulses per micron and 3 pulses per micron, respectively, yielding atwo-dimensional overlay factor of 100 pulses per spot, 25 pulses perspot and 9 pulses per spot, respectively.

In Situ Modification

Substantially the same method and apparatus discussed above can be usedfor modifying lenses in situ. This includes intraocular lenses, corneallenses, corneal contact lenses, and natural crystalline lenses. In mostinstances, the lens already has optical features, such as dioptic power,toricity and/or asphericity. This method is useful for fine tuninglenses, and provides an option to LASIK surgery.

For an in situ modification, the apparatus of FIG. 7 is used, exceptthere is no need for a lens holder 710 or means 712 for moving the lens.Rather, to the extent that the field of modification provided by thefocusing system covers only a portion of the lens being modified, thefocusing system can be changed to focus in additional regions. Withreference to FIG. 14 a layer 1410 of about 6 mm in diameter of a naturallens can be modified using the apparatus of FIG. 7. The layer 1410contains modified loci, each modified locus having from 1 to 10 sites.Typically a region of about 2 mm in diameter is modified as one scanfield. Then the lens system of the apparatus of FIG. 7 is sequentiallymoved to modify additional regions. Each region can have one or moreplanes of modified loci.

The concept of customized lens design and in situ modification can beused to achieve customized refractive corrections in living human eyesby, for example, modifying the cornea. The creation of a refractivelayer in a human cornea using methods described herein can be elected.For example, assuming a refractive index alteration of 1% in collagentissue, the exposure of a layer of 50 μm thickness inside the anteriorstroma of the cornea is sufficient to facilitate refractive correctionsof up to +/−20 diopters. A series of modified loci layer is preferablypositioned from 100 μm to 150 μm below the cornea surface. Correctionsof toric and aspheric refractive errors, as well as higher order opticalaberrations, can be achieved. The calculation of the required correctioncan be accomplished similarly to the case of customized IOL-design, bytechniques well known in the art, or by the techniques described in myaforementioned copending application Ser. No. 12/717,866, The in situtissue alteration process can be facilitated by the 2-photon microscope704, providing online procedure control, based on autofluorescenceimaging of the various cornea tissues.

In contrast to polymeric lens materials, the cornea tissue is nothomogeneous. The structure of the cornea can be visualized by 2-photonmicroscopy, utilizing a fluorescence and second harmonic generation(SHG) imaging mode.

In FIG. 14, the creation of a refractive layer inside the anterior partof a human crystalline lens is depicted. Preferably, a layer 1410 isselected, which is positioned about 100 μm below the anterior lenscapsule. The application for modifying lens tissue is especially suitedfor creating multifocalities in the presbyopic human eye to facilitatenear vision or to correct myopia (nearsightedness) or hyperopia(farsightedness) and astigmatism (toricity).

It is believed the in situ modification of cornea and lens tissues caneventually substitute LASIK-surgery, refractive lens exchange (RLE)procedures, and Phakic lens procedures providing a non-invasive,patient-friendly alternative.

Although the present invention has been described in considerable detailwith reference to the preferred versions thereof, other versions arepossible. Therefore the scope of the appended claims should not belimited to the description of the preferred versions contained therein.

1-110. (canceled)
 111. A method for modifying an optical property of a lens sized for placement in a human eye comprising the steps of: a) holding the lens external to an eye, the lens having an anterior surface, a posterior surface and an optical axis, and formed of an optical material having a first refractive index; and b) forming a contiguous three-dimensional patterned microstructure within a layer of the lens by modifying a plurality of contiguous loci in the layer by optically distributing a focused pulsed laser beam on each locus of said plurality of contiguous loci, causing a nonlinear absorption of photons by the optical material of each modified locus resulting in the optical material of the modified loci having a second refractive index that is different than the optical material before modification; wherein the contiguous three-dimensional patterned microstructure comprises a phase shifting optical structure that modifies the optical property of the lens, said phase shifting optical structure comprising a plurality of full-wave, phase-wrapped zones that compensate for optical path length differences within an array of neighboring rays.
 112. The method of claim 111, wherein the contiguous three-dimensional patterned microstructure formed in the forming step comprises a refractive structure.
 113. The method of claim 111, wherein the layer is planar.
 114. The method of claim 111, wherein the layer is substantially perpendicular to the optical axis.
 115. The method of claim 111, wherein each modified locus being right cylindrically shaped and having an axis substantially parallel to the optical axis and an axial depth of at least 5 μm.
 116. The method of claim 111, wherein the contiguous three-dimensional patterned microstructure comprises an annular ring pattern.
 117. The method of claim 111 wherein the modified optical property comprises adjusting the diopter power of the lens by at least plus or minus 0.5.
 118. The method of claim 111 wherein at least some of the loci modified during the forming step have an optical path length of from 0.1 to about 1 wavelength greater than the optical path length of a non-modified locus, wherein the wavelength is with respect to light of wavelength of 555 nm.
 119. The method of claim 111 wherein at least some of the loci modified during the forming step are configured in a substantially circular pattern around the optical axis.
 120. The method of claim 111 wherein sufficient loci are modified in the contiguous three-dimensional patterned microstructure during the forming step so that at least 90% of light projected onto the anterior surface in a direction generally parallel to the optical axis passes through at least one modified locus.
 121. The method of claim 111 wherein both the posterior and anterior surfaces of the lens are substantially planar.
 122. The method of claim 111 wherein each locus modified during the forming step has an axial depth of from 5 to 50 μm.
 123. The method of claim 111 wherein the loci modified during the forming step have an axial depth varying from about 5 to 50 μm.
 124. The method of claim 111 wherein each locus modified during the forming step has from 1 to 10 sites, the sites being arranged in an axial direction, each site being formed by a single burst of the focused laser beam.
 125. The method of claim 111 wherein the phase shifting optical structure generates an aspherical focusing effect.
 126. The method of claim 111 wherein the phase shifting optical structure generates a spherical focusing effect.
 127. A method for modifying an optical property of a disc sized for use in a human eye, the disc having an anterior surface, a posterior surface and an optical axis, and formed of an optical material having a refractive index, the method comprising the step of: forming a contiguous three-dimensional patterned microstructure within a layer of the disc by modifying the index of refraction of a plurality of contiguous loci in the layer of the disc while it is external to the eye by optically distributing a focused pulsed laser beam on each locus of said plurality of contiguous loci, causing nonlinear absorption of photons by the optical material of each modified locus, wherein the contiguous three-dimensional patterned microstructure comprises a phase shifting optical structure that modifies an optical property of the disc, said phase shifting optical structure comprising a plurality of full-wave, phase-wrapped zones that compensate for optical path length differences within an array of neighboring light rays.
 128. The method of claim 127, wherein the contiguous three-dimensional patterned microstructure formed in the forming step comprises a refractive structure.
 129. The method of claim 127, wherein the plurality of contiguous loci includes at least 1,000,000 modified loci in the layer.
 130. The method of claim 127, wherein the layer is substantially perpendicular to the optical axis.
 131. The method of claim 127, wherein each modified locus is right cylindrically shaped and has an axis substantially parallel to the optical axis and an axial depth of at least 5 μm.
 132. The method of claim 127, wherein the contiguous three-dimensional patterned microstructure formed in the forming step comprises an annular ring pattern.
 133. The method of claim 127 wherein the layer is substantially parallel to the posterior surface.
 134. The method of claim 127 wherein the layer is closer to the anterior surface than the posterior surface.
 135. The method of claim 127 wherein the laser beam has a wavelength, and the disc comprises a polymeric matrix that includes arm absorber for light of the laser beam wavelength.
 136. The method of claim 127 wherein the disc includes absorber of at least 0.01% by weight.
 137. The method of claim 127 wherein the laser has a wavelength and the method further comprises selecting a disc formed of a polymeric matrix doped with an absorber for light of the laser beam's wavelength.
 138. A method for adjusting an optical property of a disc of polymeric optical material having opposed anterior and posterior surfaces and sized for use in a human eye, the method comprising the steps of: a) emitting from a laser a pulsed beam; b) controlling the pulse rate of the beam; c) focusing the beam into a first region of the disc; d) distributing the focused beam to a plurality of contiguous loci in the first region forming a first portion of a contiguous three-dimensional patterned microstructure of modified loci having a changed index of refraction resulting from exposing each modified locus to at least one pulse of the focused beam causing a nonlinear absorption of photons in the optical material of each modified locus, wherein the contiguous three-dimensional patterned microstructure adjusts the optical property of the disc; and e) repositioning the disc relative to a focusing lens so as to focus the beam into a second region of the disc.
 139. The method of claim 138 further comprising f) distributing the focused beam to a plurality of contiguous loci in the second region forming a second portion of the contiguous three-dimensional patterned microstructure of modified loci having a changed index of refraction resulting from exposing each modified locus to at least one pulse of the focused beam causing the nonlinear absorption of photons in the optical material of each modified locus.
 140. The method of claim 139 wherein the contiguous three-dimensional patterned microstructure is configured in a planar layer in the disc, the planar layer having a thickness of about of 50 μm.
 141. The method of claim 138 wherein the disc is external to the human eye when the contiguous three-dimensional patterned microstructure of modified loci is formed.
 142. The method of claim 138 wherein the disc is an intraocular lens.
 143. The method of claim 138 wherein the focusing step comprises focusing the pulsed beam into a layer configured between the opposed surfaces.
 144. The method of claim 138 wherein the disc is internal to the eye, and wherein the loci are modified in situ.
 145. The method of claim 142 wherein the disc is part of an intraocular lens.
 146. The method of claim 138 wherein the disc provides optical correction before the step of modifying. 147-173. (canceled)
 174. A method for modifying optical properties of a lens of polymeric optical material located in a human eye comprising the steps of: a) emitting from a laser a pulsed beam; b) controlling the pulse rate of the beam; c) focusing the beam into a first region of the lens; d) distributing the focused beam to a plurality of contiguous loci in the first region forming a first portion of a contiguous three-dimensional patterned microstructure of modified loci in the first region, each modified locus in the first region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing a nonlinear absorption of photons in the optical material of each modified locus in the first region; e) focusing the beam into a second region of the lens, wherein at least a portion of the second region is different than the first region; and f) distributing the focused beam to a plurality of contiguous loci in the second region forming a second portion of the contiguous three-dimensional patterned microstructure of modified loci in the second region, each modified locus in the second region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing the nonlinear absorption of photons in the optical material of each modified locus in the second region, wherein the contiguous three-dimensional patterned microstructure comprises a phase shifting optical structure that modifies an optical property of the lens said phase shifting optical structure comprising a plurality of full-wave, phase-wrapped zones that compensate for optical path length differences within an array of neighboring light rays.
 175. The method of claim 174 wherein the disc is an intraocular lens.
 176. The method of claim 174 wherein the polymeric lens includes opposed anterior and posterior surfaces, and wherein the contiguous patterned microstructure is configured in a planar layer positioned between the opposed surfaces of the lens.
 177. A method for modifying optical properties of a disc of polymeric optical material having opposed anterior and posterior surfaces and sized for use in a human eye, the method comprising the steps of: a) emitting from a laser a pulsed beam; b) controlling the pulse rate of the beam; c) focusing the beam into a first region of the lens; d) distributing the focused beam to a plurality of contiguous loci in a first planar layer of the first region forming a first portion of a first contiguous three-dimensional patterned microstructure of modified loci in the first region, each modified locus in the first planar layer of the first region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing a nonlinear absorption of photons in the optical material of each modified locus in the first planar layer of the first region; e) distributing the focused beam to a plurality of contiguous loci in a second planar layer of the first region forming a first portion of a second contiguous three-dimensional patterned microstructure of modified loci in the first region, each modified locus in the second planar layer of the first region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing the nonlinear absorption of photons in the optical material of each modified locus in the second planar layer of the first region; f) focusing the beam into a second region of the lens, wherein at least a portion of the second region is different than the first region; g) distributing the focused beam to a plurality of contiguous loci in a first planar layer of the second region forming a second portion of the first contiguous three-dimensional patterned microstructure of modified loci in the second region, each modified locus in the first planar layer of the second region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing the nonlinear absorption of photons in the optical material of each modified locus in the first planar layer of the second region; and h) distributing the focused beam to a plurality of contiguous loci in a second planar layer of the second region forming a second portion of a second contiguous three-dimensional patterned microstructure of modified loci in the second region, each modified locus in the second planar layer of the second region having a changed index of refraction resulting from exposure to at least one pulse of the focused beam causing the nonlinear absorption of photons in the optical material of each modified locus in the second planar layer of the second region; wherein the first contiguous three-dimensional patterned microstructure modifies comprises a first phase shifting optical structure that a first optical property of the lens and the second contiguous three-dimensional patterned microstructure comprises a second phase shifting optical structure that modifies a second optical property of the lens, said first and second phase shifting optical structures each comprising a plurality of full-wave, phase-wrapped zones that compensate for optical path length differences within an array of neighboring light rays.
 178. The method of claim 177 wherein the disc is an intraocular lens.
 179. The method of claim 177 wherein the first and second planar layers have a thickness of about of 50 μm and are spaced apart from one another by at least one micron.
 180. The method of claim 177 wherein the first planar layer is spaced apart from the anterior surface by a first distance and the second planar layer is spaced apart from the anterior surface by a second distance.
 181. The method of claim 177 wherein the disc is external to the human eye when the first and second contiguous patterned microstructures of modified loci are formed.
 182. The method of claim 177 wherein the step of focusing comprises focusing the beam into planar layers configured between the opposed surfaces.
 183. The method of claim 177 wherein the disc is internal to the eye, and wherein the loci are modified in situ.
 184. The method of claim 177 wherein the disc provides optical correction before the step of modifying. 